Viral Immunotherapy in Relapsed/Refractory Multiple Myeloma (MUKeleven)

VIRel: Viral Immunotherapy in Relapsed/Refractory Multiple Myeloma - A Phase I Study to Assess the Safety and Tolerability of REOLYSIN® (Pelareorep) in Combination With Lenalidomide or Pomalidomide

This study will recruit patients currently receiving either lenalidomide or pomalidomide whose disease is relapsing. This is a dose escalation study and the aim is to determine the maximum tolerated dose (MTD) of REOLYSIN® that can be given in combination with lenalidomide or pomalidomide. The study will also investigate the safety, side effects and effectiveness of this treatment combination. Pomalidomide and lenalidomide will be evaluated separately as two separate groups.

Study Overview

• Status: Unknown
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide or Pomalidomide; Biological: REOLYSIN

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom
    • St James's University Hospital
  • Sheffield, United Kingdom
    • Sheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed with symptomatic multiple myeloma (according to IMWG 2014 criteria)
• Evaluable disease by modified IMWG criteria (i.e. by abnormal serum M protein, urinary M protein or serum free light chain assays)
• Currently receiving either lenalidomide or pomalidomide therapy, alone or in combination with other myeloma therapy, with evidence of serological or clinical disease progression as defined by IMWG criteria (2011)
• Life expectancy of ≥ 3 months
• ECOG performance status of ≤2
• Required laboratory values within 14 days prior to dose allocation:
• Absolute neutrophil count ≥ 1.0 x10^9 /L. (growth factor support is not permitted)
• Platelet count ≥ 70 x 10^9/L. (platelet support is not permitted; platelets < 70 but ≥ 25 acceptable if bone marrow is > 50% infiltrated by MM)
• Haemoglobin ≥ 8 g/dL. Blood support is permitted
• Serum bilirubin ≤ 2 x upper limit of normal (ULN)
• ALT or AST ≤ 2.5 x ULN
• Serum creatinine ≤ 2 x ULN
• Corrected calcium ≤ 2.8 mmol/l
• Negative HIV and viral (B and C) hepatitis test result within 14 days prior to dose allocation
• Able to give informed consent and willing to follow trial protocol
• Aged 18 years or over
• All participants must agree to follow the Celgene Pregnancy Prevention Programme (PPP) and participate in the counselling associated with this:
• Females of childbearing potential (FCBP) must agree to utilise two reliable forms of contraception simultaneously or practice complete abstinence for at least for 28 days prior to starting trial treatment, during the trial and for at least 28 days after trial treatment discontinuation, and even in case of dose interruption, and must agree to Celgene PPP pregnancy testing during this timeframe
• Females must agree to abstain from breastfeeding during trial participation and 28 days after trial drug discontinuation
• Males must agree to use a latex condom during any sexual contact with FCBP (or must practice complete abstinence) during the trial, including during dose interruptions and for 28 days following discontinuation from this trial even if he has undergone a successful vasectomy
• Males must also agree to refrain from donating semen or sperm while on pomalidomide including during any dose interruptions and for 28 days after discontinuation from this trial
• All participants must agree to refrain from donating blood while on trial drug including during dose interruptions and for 28 days after discontinuation from this trial

Exclusion Criteria:

• Non-secretory multiple myeloma
• Pregnant (positive pregnancy test) in line with the Celgene Pregnancy Prevention Programme or breast feeding
• Previous anti-tumour therapies including experimental agents, other than lenalidomide or pomalidomide, within 28 days of the start of protocol treatment. Steroid therapy is permitted, but must be stopped 48 hours prior to cycle 1 day 1
• Concurrent or previous malignancies (<12 months post end of treatment) at other sites, with the exception of appropriately treated localised epithelial skin or cervical cancer, or incidental histologic findings of prostate cancer (TNM stage T1a or 1b). Participants with histories (≥12 months) of other tumours, in remission and not currently on therapy, may be entered
• System corticosteroid therapy for comorbidities (i.e. medical conditions other than multiple myeloma) that cannot be stopped for the duration of the trial. Topical corticosteroid therapy is not an exclusion criterion.
• Any history of known hypersensitivity to any of the trial medications or excipients
• Active symptomatic fungal, bacterial, and/or viral infection
• Poorly controlled or serious medical or psychiatric illness that, in the Investigator's opinion, is likely to interfere with participation and/or compliance in this clinical trial
• Patients with significant cardiovascular disease (e.g. history of congestive heart failure requiring therapy (≥ NYHA Class III), presence of severe valvular heart disease, presence of an atrial or ventricular arrhythmia requiring treatment, uncontrolled hypertension, or history of QTc abnormalities)
• Radiotherapy or major surgery within 4 weeks prior to registration
• Greater than or equal to grade 2 neuropathy, with or without pain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenalidomide or pomalidomide, plus REOLYSIN; Lenalidomide capsules, oral, maximum 10mg daily on days 1-21 of 28-day cycles. OR Pomalidomide capsules, oral, maximum 1mg daily on days 1-21 of 28-day cycles. Plus (all patients): REOLYSIN® , intravenous infusion, maximum 3x10^10 TCID50 on days 1, 8, 15 and 22 of 28-day cycles.	Drug: Lenalidomide or Pomalidomide; Patients will received either lenalidomide or pomalidomide, depending on which drug they were receiving prior to the trial (they will receive the same as before).; Biological: REOLYSIN; Patients will receive Reolysin alongside either lenalidomide or pomalidomide; Other Names: Pelareorep; Reovirus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicities	Dose-limiting toxicities (DLTs), within the first cycle (until cycle 2, day 1), in order to establish the Maximum Tolerated Dose (MTD) of REOLYSIN® in combination with lenalidomide or pomalidomide, in two separate groups of participants.	After cycle 1 (28 days) of treatment. Assessed in real-time for each patient to inform dose escalation decisions.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profile of REOLYSIN® and lenalidomide	Safety will be reported based on the occurrence of SAEs, SARs and SUSARs.	Until 28 days after the last dose of trial treatment for each patient. Assessed up to 27 months.
Safety profile of REOLYSIN® and pomalidomide	Safety will be reported based on the occurrence of SAEs, SARs and SUSARs.	Until 28 days after the last dose of trial treatment for each patient. Assessed up to 27 months.
Toxicity profile of REOLYSIN® and lenalidomide	Toxicity will be reported based on adverse events, as graded by CTCAE V4.0, and determined by routine clinical assessments at each centre.	Until 28 days after the last dose of trial treatment fior each patient. Assessed up to 27 months.
Toxicity profile of REOLYSIN® and pomalidomide	Toxicity will be reported based on adverse events, as graded by CTCAE V4.0, and determined by routine clinical assessments at each centre.	Until 28 days after the last dose of trial treatment fior each patient. Assessed up to 27 months.
Response rate (stable disease or better) after 6 cycles of therapy	Measured only in patients treated at the maximum tolerated dose	Data will be collected from each patient after they have received 6 cycles of therapy, if this stage is reached. 6 cycles are expected to take 24 weeks to complete.
Maximum response within 6 cycles of therapy	Measured only in patients treated at the maximum tolerated dose	Assessed for each patient after they have received 6 cycles of treatment. 6 cycles are expected to take 24 weeks to complete.
Maximum response overall	Measured only in patients treated at the maximum tolerated dose	Assessed for each patient after they have completed treatment on the trial. Assessed up to 27 months.
Time to maximum response	Measured only in patients treated at the maximum tolerated dose	Assessed for each patient after they have completed treatment on the trial. Assessed up to 27 months.
Progression-free survival	Measured only in patients treated at the maximum tolerated dose. Participants who have not progressed at the time of analysis will be censored at the last date they were known to be alive and progression free.	Calculated for each patient from the date of registration up to first documented evidence of disease progression or death. Assessed up to 27 months.
Overall survival	Measured only in patients treated at the maximum tolerated dose. Participants who have not died at the time of analysis will be censored at the last date they were known to be alive.	Calculated for each patient from the date of registration to death. Assessed up to 27 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response biomarker profile of REOLYSIN and lenalidomide administered in combination	Biomarker profiling of the combination treatment	This will be assessed based on samples taken throughout each patient's time on the trial. Assessed up to 27 months.
Immune response biomarker profile of REOLYSIN® and pomalidomide administered in combination	Biomarker profiling of the combination treatment	This will be assessed based on samples taken throughout each patient's time on the trial. Assessed up to 27 months.

Collaborators and Investigators

• Sponsor: University of Leeds
• Collaborators: Celgene Corporation; Oncolytics Biotech; Myeloma UK
• Investigators: Principal Investigator: Gordon Cook, St. James's University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2017
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): October 1, 2021

Study Registration Dates

• First Submitted: November 16, 2016
• First Submitted That Met QC Criteria: January 6, 2017
• First Posted (Estimate): January 10, 2017

Study Record Updates

• Last Update Posted (Actual): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 21, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Pomalidomide; Lenalidomide
• Other Study ID Numbers: HM16/118

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No